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HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in bunionectomy: phase III results from the randomized EPOCH 1 study
  1. Eugene Viscusi1,
  2. Joseph S Gimbel2,
  3. Richard A Pollack3,
  4. Jia Hu4 and
  5. Gwo-Chin Lee5
  1. 1 Department of Anesthesiology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA
  2. 2 Arizona Research Center, Phoenix, Arizona, USA
  3. 3 Endeavor Clinical Trials, San Antonio, Texas, USA
  4. 4 Heron Therapeutics, Inc, San Diego, California, USA
  5. 5 Orthopaedic Surgery, Presbyterian Medical Center of Philadelphia, Philadelphia, Pennsylvania, USA
  1. Correspondence to Eugene Viscusi, Thomas Jefferson University, Philadelphia, PA 19107, USA; eugene.viscusi{at}jefferson.edu

Abstract

Background and objectives There is a need for local anesthetics that provide consistent analgesia through 72 hours after surgery. This study evaluates the use of HTX-011 (bupivacaine and meloxicam in Biochronomerpolymer technology), an extended-release, dual-acting local anesthetic, in reducing both postoperative pain over 72 hours and postoperative opioid use when compared with bupivacaine hydrochloride (HCl) and saline placebo. Inclusion of low-dose meloxicam in HTX-011 is designed to reduce local inflammation caused by surgery, potentiating the analgesic effect of bupivacaine. Previously, significant synergy has been observed with bupivacaine and meloxicam with both given locally together.

Methods EPOCH 1 was a randomized, double-blind, placebo-controlled and active-controlled phase III study in subjects undergoing a primary unilateral, distal, first metatarsal bunionectomy in which subjects received either a single intraoperative dose of HTX-011, immediate-release bupivacaine HCl or saline placebo.

Results A total of 412 subjects were dosed. The results for the primary and all four key secondary endpoints were statistically significant in favor of HTX-011. HTX-011 demonstrated superior, sustained pain reduction through 72 hours, significantly reduced opioid consumption and resulted in significantly more opioid-free subjects compared with saline placebo and bupivacaine HCl. Safety was similar across groups with fewer opioid-related adverse events observed in the HTX-011 group.

Conclusions HTX-011 demonstrated significant reduction in postoperative pain through 72 hours with significant reduction in opioid consumption and a significant increase in the proportion of opioid-free subjects compared with saline placebo and the most widely used local anesthetic, bupivacaine HCl.

Trial registration number NCT03295721.

  • lower extremity
  • postoperative pain
  • interventional pain management
  • pain medicine

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, an indication of whether changes were made, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors The authors conceived of and designed the study, analyzed and interpreted the data, drafted the manuscript and provided critical revisions to the manuscript.

  • Funding This study was supported by Heron Therapeutics, Inc.

  • Competing interests EV receives research grants from Pacira and Durect and receives consulting fees from AcelRx, Avenue, Cara, Concentric, Heron Therapeutics, Innacoll, Mallinckrodt, Merck, Neumentum, Pacira, Pfizer, Recro, Salix and Trevena; JSG has nothing to disclose; G-CL and RAP receive consulting fees from Heron Therapeutics; JH is an employee of Heron Therapeutics and receives salary and stock options.

  • Patient consent for publication Not required.

  • Ethics approval The study protocol was approved by a centralized institutional review board (Aspire IRB, Santee, California).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.

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